Dreaming is a normal human mental state with many features of dysfunctional and pathological conditions. With psychosis it shares the major symptoms of hallucination and delusion. Of the three major classes of psychosis, it is more similar to the delinum of organic mental illness than to schizophrenia or major affective disorder. With delirium, dreaming shares four major formal features: visual hallucinosis, disorientation, memory loss and confabulation. Dreaming may thus be regarded as a model psychosis which, because it is normal, can demonstrate the functional basis of major psychopathology including that which is most convincingly "organic". The main goal of the research program described in this proposal is to study REM sleep so as to account, in detailed cellular and molecular terms for the distinctive formal features of dreaming. The program proceeds at three parellel levels of analysis:" (1) quantitative phenomenological studies of dreaming as it is reported by human subjects upon spontaneous or experimental awakening from sleep; (2) cognitive tests of the mental faculties of interest (e.g. memory and attention) before, during, and after sleep and; (3) neurobiological studies of REM sleep which use cellular and molecular techniques in an animal model and which use fast MRI techniques in humans. The three levels are integrated using the specific theoretical models that have been developed in this laboratory over the past thirty years. As one example of our paradigm and its results, consider the prominent and robust cognitive feature called dream bizarreness. As a result of our quantitative analysis of dream reports, we have developed a reliable method of detecting this dream feature and have been able to show that it is sensitive to discontinuity and/or incongruity of dream persons, places, times and actions. This orientational instability can now be modeled and investigated at several levels;" at the cognitive level we are studying covert attention (an orienting function) and semantic priming (on orientating function). We have recently shown that dream eports can be reliably analyzed using a graph theory approach that reliably shifts in visual attention as they are experienced subjectivity. At the neurophysiological level we are investigating the PGO system as it functions in the orienting response in cats; in human studies we are looking at shifts in the spontaneous activity of the posterior and interior attentional systems during REM sleep and waking. The direct clinical implications of this work include; understanding and medical control of sleep disorders such as narcolepsy and the REM sleep behavior disorder; understanding and medical control of such symptomatic states as panic anxiety, attention deficit disorder, major affective disorder (especially depression) and of delirium itself. More indirect but equally important implications relate to development of a general state space model that can explain the entire spectrum of normal and pathological mental states in functional terms.